One-year safety and effectiveness of insulin degludec in patients with diabetes mellitus in routine clinical practice in India-TRUST (Tresiba real-world use study).

Objective: This post-authorization safety study (PASS) was conducted to evaluate the long-term safety and effectiveness of insulin degludec in patients with diabetes mellitus (DM) requiring insulin therapy in routine clinical practice in India. Methods: Data on glycated hemoglobin (HbA1c) and adverse events (AEs) were collected up to 12 months after insulin degludec initiation. Results: A total of 1057 adult patients with DM were enrolled, including 60.07% males with the mean duration of 22.2 ± 21.90 years with type 1 DM and 10.1 ± 7.37 years with type 2 DM and the mean HbA1c of 9.6 ± 1.9%. Insulin degludec was prescribed to improve HbA1c and fasting plasma glucose (FPG). Insulin degludec daily dose was increased from 14.8 ± 8.0 U to 18.0 ± 9.46 U over 12 months resulting in a significant decrease of HbA1c by 1.8 ± 1.68% compared with baseline. There were 84 events of confirmed hypoglycemia in 51 patients during the 12-month follow-up period, and 44 AEs were reported in 2.6% of patients, of which 2 AEs were serious and unrelated to the drug. Conclusion: Insulin degludec is well tolerated in patients with DM. It improves glycemic control with reduced HbA1c, FPG, and postprandial glucose, with a low risk of hypoglycemia.

Bi-maxillary Protrusion: An Orthodontic Management.

Bi-maxillary protrusion is a condition with protrusive and proclined upper and lower incisors and the patient is not able to close lips without strain. The presented case reported with the chief complaint of forwardly placed teeth, with skeletal class II malocclusion, and Angle's class I malocclusion with protrusive and forwardly placed upper and lower incisors. The treatment was performed with the extraction of all first premolars and retraction under absolute anchorage. The retraction of upper and lower lips of about 3 mm and 3.5 mm was achieved respectively and the patient was able to close lips without strain. With proper anchorage preparation, bi-maxillary protrusion can be successfully managed orthodontically.

Influence of learning-style preferences in academic performance in the subject of human anatomy: an institution-based study among preclinical medical students.

Purpose: The present study was conducted to find the preferred mode of learning among first-year preclinical students and compare the preferred mode of learning with sex, faculty of students, and academic performance of the students using the VARK questionnaire. Methods: A cross-sectional study was done among 142 first-year Bachelor of Medicine-Bachelor of Surgery and Bachelor of Dental Surgery students from February to May 2018. Demographic data and various academic performance marks were recorded for each individual. VARK (visual, aural, read/write and kinesthetic) questionnaire version 7.8 was administered to calculate the score of each component. Mean VARK scores were calculated and each student classified by their preferred mode of learning. The preferred mode of learning was compared with sex, nationality, faculty of students, and academic performance using χ 2, unpaired t-tests, and the Mann-Whitney U test. P<0.05 was taken as statistically significant for comparison. Results: A majority of the students (53.52%) were multimodal. The most common multimodal mode of preference was bimodal (26.06%), while the most common unimodal preference was kinesthetic (29.06%). Total V score, K score, and VARK score were higher among males, while A and R scores were higher among females. The K score (7.96±2.35 in males and 6.96±2.43 in females) differed significantly (P=0.019) between male and female subjects. More subjects with higher scores in the theory exam of anatomy were unimodal learners (53.8%) compared to multimodal learners (46.2%). Conclusion: From this study, it can be concluded that undergraduate students were diverse in their learning styles, but most were multimodal. Though learning styles were found to vary by sex, nationality, and academic performance, differences were not statistically significant.

Rice and chickpea GDPDs are preferentially influenced by low phosphate and CaGDPD1 encodes an active glycerophosphodiester phosphodiesterase enzyme.

KEY MESSAGE: Rice and chickpea GDPD s are transcriptionally influenced by mineral deficiencies; especially, by phosphate starvation and CaGDP1 encodes an active glycerophosphodiester phosphodiesterase enzyme. Glycerophosphodiester phosphodiesterases (GDPDs) are enzymes involved in the degradation of glycerophosphodiesters into sn-glycerol-3-phosphate and corresponding alcohols. These phospholipid remodeling genes have been suggested to play important roles in phosphate homeostasis. However, comprehensive information about the role of GDPDs under low phosphate (P) and other nutrient deficiencies (N, K, Fe, Zn) in rice and chickpea is missing. Here, we identified 13 OsGDPDs and 6 CaGDPDs in rice and chickpea, respectively, and partly characterized their roles in multiple nutrient stresses. Expression profiling after 7 and 15 days of deficiency treatments revealed unique and overlapping differential expression patterns of OsGDPDs and CaGDPDs under different nutrient stresses. Principal component analysis on the expression patterns of OsGDPDs and CaGDPDs revealed their preferential role in P starvation. Some of the GDPDs were also induced by N, K, Fe and Zn deficiency in temporal manner in both crops suggesting their roles in multiple nutrient stresses. Biochemical characterization of highly responsive chickpea GDPD, CaGDPD1, confirmed its in vitro GDPD activity and revealed its optimal temperature, pH and cofactor requirements. Further, CaGDPD1 showed its accumulation in ER and endomembranes. We hereby propose CaGDPD1 and various OsGDPDs as low P responsive marker genes in chickpea and rice, respectively. Our data uphold role of GDPDs in multinutrient responses and suggest them as candidates for rice and chickpea improvement for tolerance to various nutrient deficiencies.

Clinical experience with insulin detemir, biphasic insulin aspart and insulin aspart in people with type 2 diabetes: Results from the Tamil Nadu cohort of the A1chieve study.

BACKGROUND: The A1chieve, a multicentric (28 countries), 24-week, non-interventional study evaluated the safety and effectiveness of insulin detemir, biphasic insulin aspart and insulin aspart in people with T2DM (n = 66,726) in routine clinical care across four continents. MATERIALS AND METHODS: Data was collected at baseline, at 12 weeks and at 24 weeks. This short communication presents the results for patients enrolled from Tamil Nadu, India. RESULTS: A total of 2221 patients were enrolled in the study. Four different insulin analogue regimens were used in the study. Patients had started on or were switched to biphasic insulin aspart (n = 1707), insulin detemir (n = 270), insulin aspart (n = 85), basal insulin plus insulin aspart (n = 79) and other insulin combinations (n = 80). At baseline glycaemic control was poor for both insulin naïve (mean HbA1c: 9.2%) and insulin user (mean HbA1c: 9.2%) groups. After 24 weeks of treatment, both the groups showed improvement in HbA1c (insulin naïve: -1.7%, insulin users: -1.7%). SADRs including major hypoglycaemic events did not occur in any of the study patients. CONCLUSION: Starting or switching to insulin analogues was associated with improvement in glycaemic control with a low rate of hypoglycaemia.

Evaluation of efficacy and tolerability of Losartan and Ramipril combination in the management of hypertensive patients with associated diabetes mellitus in India (LORD Trial).

AIM: The study was conducted to evaluate efficacy and tolerability of fixed dose combination (FDC) of Losartan and Ramipril in the management of mild to moderate hypertensive Native Asian Indian patients with associated diabetes mellitus. The secondary objective was to evaluate the efficacy of the combination in reducing microalbuminuria. MATERIAL AND METHODS: The study was an open, non-comparative, multicentric clinical trial conducted in seven Indian centres in 315 eligible patients. All the patients were treated with Losartan 50 mg + Ramipril 2.5 mg or Losartan 50 mg + Ramipril 5 mg once a day in 12 weeks and consisted of a total of eight visits. RESULTS: The mean age of patients was 52.93 years (range 45 - 60 years). Of the total patients, 62.86% were males and 37.14% were females. The mean prestudy systolic blood pressure was 160.56 +/- 14.44 which was significantly reduced to 126.85 +/- 9.78 at the end of 12 weeks (P < 0.001). Similarly the mean diastolic blood pressure was 98.91 +/- 8.33 at baseline (stage I) which was significantly reduced to 79.82 +/- 5.42 at the end of 12 weeks (P < 0.001). A mean fall of 33.72 mmHg in systolic blood pressure and the mean fall of 19.10 mmHg was observed in systolic and diastolic blood pressure respectively at the end of the treatment which was statistically highly significant (P < 0.001). The JNC-VII goal of blood pressure < 130/80 was achieved in 79.05% patients after the treatment which losartan and ramipril combination only. Microalbuminuria (urinary albumin excretion > 30 but < 300 mg/day) was seen in 83/250 (33.2%) patients and 135 (54%) patients had clinical proteinuria (albuminuria) at baseline. At the end of the therapy 20.8% patients achieved normoalbuminuria. Good to excellent efficacy response was reported in 98.09% patients and 98.41% patients reported good to excellent tolerability to the treatment. CONCLUSION: The fixed dose combination of Losartan and Ramipril showed good to excellent efficacy response in 98.10% patients and achieved a target blood pressure of 130/80 mmHg in 79.05% patients in 12 weeks. The combination reduced the urinary albumin excretion in majority of the patients with microalbuminuria and proteinuria (the major marker of nephropathy).

The enhanced in vitro hematopoietic activity of leridistim, a chimeric dual G-CSF and IL-3 receptor agonist.

The in vitro activity of leridistim was characterized for cell proliferation, generation of colony-forming units (CFU) and differentiation of CD34+ cells. In AML-193.1.3 cells, leridistim exhibited a significant increase in potency compared to rhG-CSF, SC-65303 (an IL-3 receptor agonist) or an equimolar combination of rhG-CSF and SC-65303. CFU-GM assays demonstrated that at 50% of the maximum response, the relative potency of leridistim was 12-fold greater than the combination of rhG-CSF and rhIL-3 and 44-fold more potent than rhG-CSF alone. In multi-lineage CFU assays, a combination of erythropoietin (rhEPO) and leridistim resulted in greater numbers of BFU-E, CFU-GEMM and CFU-Mk than rhEPO alone. Ex vivo culture of peripheral blood or bone marrow CD34+ cells with leridistim substantially increased total viable cells over cultures stimulated with rhG-CSF, SC-65303, or a combination of rhG-CSF and SC-65303. Culture with leridistim, resulted in a greater increase in myeloid (CD15+/CD11b+), monocytic (CD41-/CD14+) and megakaryocytic (CD41+/CD14-) precursor cells without depleting the progenitor pool (CD34+/CD15-/CD11b-). These results demonstrate that leridistim is a more potent stimulator of hematopoietic proliferation and differentiation than the single receptor agonists (rhG-CSF and SC-65303) either alone or combined. These unique attributes suggest that leridistim may enhance hematopoietic reconstitution following myelosuppressive chemotherapy.

Promegapoietin, a family of chimeric growth factors, supports megakaryocyte development through activation of IL-3 and c-Mpl ligand signaling pathways.

OBJECTIVE: The signaling pathways induced by promegapoietin (PMP), a family of chimeric growth factors that activate the human IL-3 and c-Mpl receptors, were investigated. METHODS: The biological activity of PMP was examined by receptor binding, cell proliferation, ex vivo expansion of hematopoietic progenitor cells, and in vivo production of platelets. The activation of signaling pathways was examined by Western blot and Northern blot analyses. RESULTS: Two PMP molecules, PMP-1 and PMP-1a, induced proliferation of cells expressing the IL-3 receptor, c-Mpl, or both receptors and bound to the IL-3 receptor and c-Mpl with high affinity. Ex vivo expansion assays using human bone marrow CD34(+) cells suggested that PMP-1 induced greater total cellular expansion as well as expansion of CD41(+) megakaryocytic precursor cells than IL-3 or c-Mpl ligand alone. Subcutaneous administration of 50 microg/kg of PMP-1 for 10 days to rhesus monkeys resulted in increased platelet production in vivo from a baseline of 357 +/- 45 x 10(3) cells/mL to 1376 +/- 151 x 10(3) cell/mL. PMP-1 induced phosphorylation of the beta(c) subunit of IL-3 receptor and c-Mpl, JAK2, and STAT5b, but not STAT3. PMP-1 induced greater expression of Pim-1, c-Myc, and cyclin D2 than did either an IL-3 receptor agonist or c-Mpl receptor agonist alone. The magnitude of induction of early response genes was similar for PMP and the coaddition of IL-3 receptor agonist and c-Mpl receptor agonist. CONCLUSION: PMP combines the biological activities of IL-3 and c-Mpl ligand in a single molecule that can simultaneously activate signaling pathways induced by both these ligands.

Promegapoietin-1a, an engineered chimeric IL-3 and Mpl-L receptor agonist, stimulates hematopoietic recovery in conventional and abbreviated schedules following radiation-induced myelosuppression in nonhuman primates.

Promegapoietin-1a (PMP-1a), a multifunctional agonist for the human interleukin 3 and Mpl receptors, was evaluated for its ability to stimulate hematopoietic reconstitution in nonhuman primates following severe radiation-induced myelosuppression. Animals were total body x-irradiated (250 kVp) to 600 cGy total midline tissue dose. PMP-1a was administered s.c. in several protocols: A) daily (50 microg/kg) for 18 days; B) nine doses (5 microg/kg) every other day for 3 weeks; C) a single high dose (100 microg/kg) at 20 hours, or D) a single high dose (100 microg/kg) at 1 hour following TBI. The irradiation controls received 0.1% autologous serum for 18 consecutive days. Hematopoietic recovery was assessed by bone marrow clonogenic activity, peripheral blood cell nadirs, duration of cytopenias, time to recovery to cellular thresholds, and requirements for clinical support. PMP-1a, irrespective of administration schedule, significantly improved all platelet-related parameters: thrombocytopenia was eliminated, the severity of platelet nadirs was significantly improved, and recovery of platelet counts to > or =20,000/miccrol was significantly reduced in all PMP-1a-treated cohorts. As a consequence, all PMP-1a-treated cohorts were transfusion-independent. Neutrophil regeneration was augmented in all treatment schedules. Additionally, all PMP-1a-treated cohorts showed an improvement in red blood cell nadir and recovery. PMP-1a in conventional or abbreviated schedules induced significant thrombopoietic regeneration relative to the control cohort, whereas significant improvement in neutrophil recovery was schedule-dependent in radiation-myelosuppressed nonhuman primates.

[Infrequent deletion in 67 codon in HIV reverse transcriptase in antiretroviral treatment failure]. / Deleción infrecuente en el codón 67 del gen de la transcriptasa reversa de HIV en falla al tratamiento antirretroviral.

We present a clinical case of antiretroviral treatment failure with appearance of mutations demonstrated by genotyping. We also show the evolution of the pattern of mutations that confers resistance to protease and reverse transcriptase inhibitors along with changes in the scheme of drugs indicated to the patient. A deletion was found in codon 67 of the TR gen, along with a novel resistance model to AZT pointing out the benefits of the detection of antiviral resistance by sequencing (genotyping).

Synthesis and release of B-lymphocyte stimulator from myeloid cells.

B-lymphocyte stimulator (BLyS) is a recently identified novel member of the tumor necrosis factor ligand superfamily shown to exist in a membrane-bound and soluble form. BLyS was found to be specifically expressed on cells of myeloid lineage and to selectively stimulate B-lymphocyte proliferation and immunoglobulin production. The expression of a cytokine involved in potentiation of humoral immune responses, such as BLyS, is expected to be strictly controlled. The goal of the present study was to examine regulation of BLyS levels in monocytic cells in response to cytokines and during their differentiation to macrophages and dendritic cells. The presence of BLyS on the cell surface and in the culture medium of both normal blood monocytes and on tumor cells of myelomonocytic origin was demonstrated. BLyS gene expression and levels of membrane-associated and soluble BLyS were found to be regulated by cytokines, in particular interferon (IFN)-gamma and to a lesser extent interleukin-10 (IL-10). The expression of BLyS on monocyte membranes was retained following differentiation into macrophages, but detection on the surface of monocyte-derived dendritic cells required stimulation with IFN-gamma. Both IFN-gamma and IL-10 enhanced the release of soluble BLyS that was active in B-cell proliferation assays. Cells transfected with BLyS complementary DNA mutated in a predicted cleavage site failed to release BLyS into the culture medium, thereby suggesting that soluble BLyS was derived from the membrane form. These results provide further support for an important role for BLyS expressed in myeloid cells in B-cell expansion and antibody responses.

BLyS BINDS TO B CELLS WITH HIGH AFFINITY AND INDUCES ACTIVATION OF THE TRANSCRIPTION FACTORS NF-kappaB AND ELF-1.

B lymphocyte stimulator (BLyS) is a novel member of the TNF family of proteins expressed by myeloid cells as membrane-bound and soluble forms. BLyS was shown to act specifically on B cells, inducing proliferation and immunoglobulin production both in vitro and in vivo. The present study was undertaken to characterize binding of radiolabeled BLyS to its cognate receptor on human B lymphocytes and examine intracellular events initiated by BLyS binding. Similar to other TNF family members, BLyS is present in solution as a homotrimer as determined by gel filtration chromatography and light scattering analysis. BLyS binding to B cells is specific as other TNF family members tested did not compete for(125)I-BLyS binding. Analysis of equilibrium binding of(125)I-labeled BLyS to purified human tonsillar B cells demonstrated saturable binding. Scatchard analysis of the binding data revealed a single class of high-affinity binding on human B cells with approximately 2600 binding sites per cell and an apparent dissociation constant (K(D)) of about 0.1 nM. In addition we report that BLyS binding to B cells results in the activation of NF-kappaB and the Ets family transcription factor, ELF-1, and in the induction of mRNA for Polo-like kinase (PLK).

Polyoma virus JC DNA detection by polymerase chain reaction in CSF of HIV infected patients with suspected progressive multifocal leukoencephalopathy.

Several studies had previously demonstrated the high sensitivity and specificity of JCV DNA detection in CSF by PCR. This paper reported the implementation of a simple PCR procedure to detect JCV in the CSF in a cohort of HIV-1 infected patients from Argentina. Years ago, the confirmatory diagnosis of this disease was made by in-situ hybridization or immunohistochemistry techniques on brain biopsies. The PCR procedure described here improves the diagnosis of PML because it is simple and noninvasive, and allows the differential diagnosis of PML from other neurological syndromes associated with AIDS. Many recent studies report a significant benefit of combined antiretroviral therapy on the survival of HIV patients without clear neurological improvements. A negative correlation has been described between the concentration of JCV in the CSF and survival time in HIV-1 infected patients, and the level of immune depression may influence JCV replication. This suggests that a single CSF JCV viral load determination during the course of PML disease progression may be of prognostic value for managing HIV patients.

Deleción infrecuente en el codón 67 del gen de la transcriptasa reversa de HIV en falla al tratamiento antirretroviral. / [Infrequent deletion in 67 codon in HIV reverse transcriptase in antiretroviral treatment failure]

We present a clinical case of antiretroviral treatment failure with appearance of mutations demonstrated by genotyping. We also show the evolution of the pattern of mutations that confers resistance to protease and reverse transcriptase inhibitors along with changes in the scheme of drugs indicated to the patient. A deletion was found in codon 67 of the TR gen, along with a novel resistance model to AZT pointing out the benefits of the detection of antiviral resistance by sequencing (genotyping).

BLyS: member of the tumor necrosis factor family and B lymphocyte stimulator.

The tumor necrosis factor (TNF) superfamily of cytokines includes both soluble and membrane-bound proteins that regulate immune responses. A member of the human TNF family, BLyS (B lymphocyte stimulator), was identified that induced B cell proliferation and immunoglobulin secretion. BLyS expression on human monocytes could be up-regulated by interferon-gamma. Soluble BLyS functioned as a potent B cell growth factor in costimulation assays. Administration of soluble recombinant BLyS to mice disrupted splenic B and T cell zones and resulted in elevated serum immunoglobulin concentrations. The B cell tropism of BLyS is consistent with its receptor expression on B-lineage cells. The biological profile of BLyS suggests it is involved in monocyte-driven B cell activation.

Megakaryocyte ex vivo expansion potential of three hematopoietic sources in serum and serum-free medium.

Megakaryocytes (MK) were expanded from purified human CD34+ cells obtained from three sources, bone marrow (BM), mobilized peripheral blood progenitor cells (PB), and umbilical cord (UC) blood. CD34+-selected cells were cultured for 12 days with 10 ng/ml thrombopoietin (TPO), 10 ng/ml IL-3, 10 ng/ml TPO + 10 ng/ml IL-3, or 200 ng/ml promegapoietin (PMP), a chimeric dual agonist of the c-Mpl and human IL-3 receptors. MK production was compared in serum-free versus human serum-supplemented liquid media. PMP and the combination of TPO and IL-3 (TPO + IL-3) increased MK production similarly. Culturing CD34+ cells with PMP in serum-free medium resulted in a twofold increase in MK yield compared with serum-supplemented medium. CD34+ cells from UC proliferated more than those from either BM or PB in liquid culture, resulting in much greater MK production under all conditions. Phenotypic analysis of the uncultured CD34+ cells showed that BM had a higher frequency of CD34+/CD41+ cells than PB or UC. TPO + IL-3 or PMP produced larger and greater numbers of BFU-MK and CFU-MK per seeded CD34+/CD41+ cell from UC than from either BM or PB. Thus, although uncultured CD34+-selected BM cells contained a higher frequency of committed mature MK progenitors, UC CD34+ cells had a greater proliferative capacity and, therefore, were more productive. PMP induced megakaryocytopoietic activity comparable to that achieved with TPO + IL-3 and may be useful for ex vivo expansion of MK for clinical trials.

Nitric oxide is involved in stimulation of tumor growth.

The immune system can inhibit or stimulate tumor growth. Peritoneal cells (PEG) from MM3 mammary tumor-bearing mice (TBM) displayed enhanced capacity to produce nitric oxide (NO) upon stimulation with LPS plus IFN-gamma, as compared to normal mice. The addition of L-Arginine (L-Arg) increased NO release by TBM-PEC but not by normal PEG; this increase could be reversed with N-G-nitro-L-arginine methyl ester (L-NAME). This inhibitor, given systemically, decreased MM3 tumor growth but not lung metastasis. Tumor retardation was associated with inhibition of angiogenesis induced by spleen cells. Conversely, L-Arg potentiated vascular response but not tumor growth. In conclusion, NO synthesis is up regulated in PEC during MM3 tumor progression sustaining tumor growth by mediating the angiogenic cascade.

Regulated expression and release of the IL-1 decoy receptor in human mononuclear phagocytes.

The aim of this study was to investigate the expression and release of the IL-1 type II decoy receptor (R) in mononuclear phagocytes, which play a central role in immune and chronic inflammatory reactions. Human monocytes expressed both type I and type II R transcripts, the latter being two- to threefold more represented. By cross-linking and Ab blocking, the predominant surface IL-1-binding molecule was the decoy RII. IL-4, IL-13, and dexamethasone induced RI and RII transcripts and augmented the number of IL-1-binding sites with no modification of Kd values. The induced surface receptor was identified as the decoy RII. These stimuli induced the release of a soluble R with a m.w. of approximately 60 kDa, of which N-glycosylation contributed 22 kDa compared with 45 kDa released from polymorphonuclear leukocytes, of which N-glycosylation contributed 15 kDa. IL-13 and dexamethasone induced a release of 24 ng/ml/2 x 10(7) cells (from 8.7 to 43.2 ng/ml) and 25.6 ng/ml/2 x 10(7) cells (from 9.7 to 36.8 ng/ml) of decoy RII in 18 h, respectively (six donors). Thus, for instance, IL-13-treated (18 h) cells expressed 3.5 x 10(3) sites/cell and released 12 x 10(3) decoy RII/cell. The released decoy RII from monocytes bound IL-1apha and IL-1 receptor antagonist 30- and 2-fold less avidly than IL-1beta, respectively. In vitro-matured, monocyte-derived macrophages showed higher levels of surface expression and release of the IL-1 decoy RII. The results show that, on exposure to diverse molecules with anti-inflammatory properties, mononuclear phagocytes express and release copious amounts of a novel version of the soluble IL-1 decoy RII.

Increased soluble interleukin-1 type II receptor concentrations in postoperative patients and in patients with sepsis syndrome.

Plasma interleukin-1 (IL-1) activity is modulated in part through the simultaneous appearance of several inhibitors of IL-1 action, including interleukin-1 receptor antagonist (IL-1ra) and the soluble IL-1 type II receptor (IL-1RII). However, little is known concerning the plasma appearance of these inhibitors in patients following operative trauma or those with sepsis syndrome. In the present report, plasma IL-1beta, IL-1ra, and soluble IL-1RI and IL-1RII concentrations were evaluated in 118 patients with sepsis syndrome or after elective operative trauma. Plasma concentrations of IL-1ra increased significantly following elective operative repair of thoraco-abdominal and abdominal aortic aneurysms, and after bowel resection for inflammatory bowel disease, but did not increase after laparoscopic cholecystectomy. Plasma IL-1ra levels were also elevated in patients with sepsis syndrome. In contrast, soluble IL-1RII levels were only increased in patients after operative repair of thoraco-abdominal aortic aneurysms and in sepsis syndrome, whereas concentrations were unaffected by the other more modest surgical procedures. Plasma IL-1RI concentrations decreased in all postoperative patients in the first 24 hours after surgery. We conclude that both plasma IL-1ra and soluble IL-1RII concentrations often increase in sepsis and following some operative trauma. Less severe operative trauma increases the plasma concentration of only IL-1ra, whereas both IL-1ra and soluble IL-1RII are increased in patients with sepsis syndrome or following thoraco-abdominal aneurysm repair.